Biochemical and physiological functions of renal cells are studied concurrent with, or following, in vitro exposure to nephrotoxic chemicals. The elicited effects are correlated with morphological alterations to assess subcellular mechanisms of action. Parallel studies are conducted in intact animals (in vivo) to assure the relevancy of the effects studied in vitro and to determine the role of extrarenal factors in the development of chemical nephropathy. The in vitro environment (e.g., pH, electrolytes, cofactors, energy substrates) is manipulated to suggest biochemical mechanisms of action.